Wang Yifei, Wang Xiaolong, Li Wenhao, Huang Hanwen, Di Chenyu, Yang Qifeng
Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Department of Breast Surgery, General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China; Biological Resource Center, Qilu Hospital of Shandong University, Jinan, Shandong, China; Research Institute of Breast Cancer, Shandong University, Jinan, Shandong, China.
J Ethnopharmacol. 2025 May 12;347:119723. doi: 10.1016/j.jep.2025.119723. Epub 2025 Apr 1.
Trametes robiniophila Murr (Huaier), a traditional Chinese medicine (TCM), has shown promising effects as a complementary therapy in the treatment of multiple kinds of cancers.
This study aimed to systematically evaluate whether Huaier could enhance the antitumor effects of palbociclib, a highly selective CDK4/6 inhibitor.
A breast cancer xenograft mouse model was constructed to assess the anticancer effects of Huaier and palbociclib. Transcriptomic analysis was performed to identify the differentially expressed genes and associated pathways. Flow cytometry, immunofluorescence and immunohistochemical staining were then conducted to observe the infiltration of immune cells in the tumor microenvironment (TME). The composition of the gut microbiota was explored through 16S rDNA sequencing, and a pseudosterile mouse model was established to verify the contribution of the gut microbiota to the antitumor effects of Huaier and palbociclib.
Oral administration of Huaier enhanced the antitumor effects of palbociclib in breast cancer. Transcriptomic analysis of tumor tissues revealed that the differentially expressed genes were related to immune functions. Indeed, the addition of Huaier to palbociclib therapy further increased the ratio of CD8/CD3 T cells and the abundance of GzmBCD8 T cells in the TME. Mechanistically, sequencing of 16S rDNA revealed that Huaier reshaped the gut microbiota composition in favor of Akkermansia, which positively modulated antitumor immune responses. The pseudosterile mouse model verified the necessity of the gut microbiota for the synergistic effect of Huaier on palbociclib. Furthermore, butyrate, a metabolite of Akkermansia, synergized with palbociclib to suppress tumor progression and promote the infiltration of CD8 T cells in the TME.
Our data suggested that Huaier augmented the antitumor effects of palbociclib by increasing the abundance of Akkermansia in gut microbiota, which contributed to the enhancement of anti-tumor immunity. Consequently, combining palbociclib with Huaier may serve as a promising strategy for the treatment of breast cancer.
槐耳菌（槐耳）是一种传统中药，在多种癌症的辅助治疗中显示出有前景的效果。
本研究旨在系统评估槐耳是否能增强高度选择性的细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂哌柏西利的抗肿瘤作用。
构建乳腺癌异种移植小鼠模型以评估槐耳和哌柏西利的抗癌作用。进行转录组分析以鉴定差异表达基因及相关通路。随后进行流式细胞术、免疫荧光和免疫组织化学染色，以观察肿瘤微环境（TME）中免疫细胞的浸润情况。通过16S核糖体DNA测序探索肠道微生物群的组成，并建立无菌小鼠模型以验证肠道微生物群对槐耳和哌柏西利抗肿瘤作用的贡献。
口服槐耳增强了哌柏西利对乳腺癌的抗肿瘤作用。肿瘤组织的转录组分析表明，差异表达基因与免疫功能相关。事实上，在哌柏西利治疗中添加槐耳进一步增加了TME中CD8/CD3 T细胞的比例和颗粒酶B+CD8 T细胞的丰度。机制上，16S rDNA测序显示槐耳重塑了肠道微生物群组成，有利于阿克曼氏菌，其正向调节抗肿瘤免疫反应。无菌小鼠模型验证了肠道微生物群对槐耳与哌柏西利协同作用的必要性。此外，阿克曼氏菌的代谢产物丁酸盐与哌柏西利协同抑制肿瘤进展并促进CD8 T细胞在TME中的浸润。
我们的数据表明，槐耳通过增加肠道微生物群中阿克曼氏菌的丰度增强了哌柏西利的抗肿瘤作用，这有助于增强抗肿瘤免疫力。因此，将哌柏西利与槐耳联合使用可能是治疗乳腺癌的一种有前景的策略。
